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Sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists and the risk for cardiovascular outcomes in routine care patients with diabetes across categories of cardiovascular disease
Open accessAbstract
BACKGROUND: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in placebo-controlled trials of patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD). OBJECTIVE: To evaluate whether SGLT2 inhibitors and GLP-1 RAs are associated with differential cardiovascular benefit among T2D patients with and without CVD. DESIGN: Population-based cohort study. SETTING: Medicare and 2 U.S. commercial claims data sets (April 2013 to December 2017). PARTICIPANTS: 1:1 propensity score-matched adult T2D patients with and without CVD (52 901 and 133 139 matched pairs) initiating SGLT2 inhibitor versus GLP-1 RA therapy. MEASUREMENTS: Primary outcomes were myocardial infarction (MI) or stroke hospitalization and hospitalization for heart failure (HHF). Pooled hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, with 95% CIs, controlling for 138 preexposure covariates. RESULTS: The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with a slightly lower risk for MI or stroke in patients with CVD (HR, 0.90 [95% CI, 0.82 to 0.98]; RD, -2.47 [CI, -4.45 to -0.50]) but similar risk in those without CVD (HR, 1.07 [CI, 0.97 to 1.18]; RD, 0.38 [CI, -0.30 to 1.07]). The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with reductions in HHF risk regardless of baseline CVD in patients with CVD (HR, 0.71 [CI, 0.64 to 0.79]; RD, -4.97 [CI, -6.55 to -3.39]) and in those without CVD (HR, 0.69 [CI, 0.56 to 0.85]; RD, -0.58 [CI, -0.91 to -0.25]). LIMITATION: Treatment selection was not randomized. CONCLUSION: Use of SGLT2 inhibitors versus GLP-1 RAs was associated with consistent reductions in HHF risk among T2D patients with and without CVD, although the absolute benefit was greater in patients with CVD. There were no large differences in risk for MI or stroke among T2D patients with and without CVD. PRIMARY FUNDING SOURCE: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School.
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“These conclusions are further supported by observational data from a large populationbased cohort study in the U.S., which showed that SGLT2i reduced HHF compared with GLP-1 RA in people both with CVD (hazard ratio [HR] 0.71; 95% CI 0.64, 0.79) and without CVD (HR 0.69; 95% CI 0.56, 0.81).”
From Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2022) · cites this paper as [261]
Experimental — accuracy not yet measuredIn the citing paper
“but data from a real-world cohort of 557 109 individuals suggested that SGLT2is and GLP-1RAs provide comparable protection against atherosclerotic CVD in people with T2DM.53”
From Benefits of GLP-1 (Glucagon-Like Peptide 1) Receptor Agonists for Stroke Reduction in Type 2 Diabetes: A Call to Action for Neurologists (2022) · cites this paper as [53]
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“Conclusion: Use of SGLT2 inhibitors versus GLP-1 RAs was associated with consistent reductions in HHF risk among T2D patients with and without CVD, although the absolute benefit was greater in patients with CVD.”
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Metadata
- Authors
- Patorno, E., Htoo, P. T., Glynn, R. J., Schneeweiss, S., Wexler, D. J., Pawar, A., Bessette, L. G., Chin, K., Everett, B. M., & Kim, S. C.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- ORCID
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2021-11
- Volume
- 174
- Issue
- 11
- Pages
- 1528-1541
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- PMC
- PMC8969214
- OpenAlex
- W3201795055
- Cited by
- 103
- References
- 44
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 24 · 2023: 27 · 2022: 23 · 2021: 3
- FWCI
- 14.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (K08AG055670)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- SGLT2 inhibitors, GLP-1 receptor agonists, type 2 diabetes, cardiovascular disease, cardiovascular outcomes, myocardial infarction, stroke, heart failure hospitalization, real-world evidence, antidiabetic drug comparison, Medicare beneficiaries, cardiovascular risk reduction, propensity score matching, claims data, glycemic control
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Sodium-Glucose Transporter 2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Heart Failure, Hospitalization, Humans, Male, Middle Aged, Myocardial Infarction, United States, Cohort Studies, Matched-Pair Analysis, Stroke
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